We have found that the plasma binding of the antiarrhythmic drug, lidocaine, varies widely in health and disease and that this seems largely related to the plasma concentration of alpha 1 acid glycoprotein (AAG). Further in patients with myocardial infarction (MI) we have confirmed that plasma lidocaine levels accumulate during a constant infusion, but a rise in AAG and increased plasma binding significantly attenuated accumulation in terms of free drug. This suggests that altered lidocaine binding may affect the kinetics of lidocaine, especially with respect to the free (and presumed active) concentration. We propose to study the kinetics of blood plasma and free lidocaine after oral and i.v. administration in health and in patients with MI, renal disease, heart failure, cirrhosis and epilepsy treated with enzyme inducers--situations in which lidocaine disposition is altered--and relate these changes to plasma binding and AAG. In addition these data can be used to estimate liver blood flow. As a result, we will not only be able to devise more rational dosage regimens for lidocaine therapy, but also use lidocaine as a model drug for predicting the effects of altered liver blood flow, intrinsic clearance and binding in blood on the kinetics of ther highly extracted compounds.